Nerve damage in patients will often not regenerate naturally, and can lead to permanent loss of sensitivity and function. For this reason, surgical and therapeutic interventions to promote repair can be desirable.
International patent application WO2004/087231 describes a self-aligning tissue growth guide. The guide comprises a core of a biopolymer matrix which is fixed to an outer sheath at two points. The core is seeded with cells, which generate a mechanical contractile force leading to self-alignment of the cells within the core. This produces a cellular guidance substrate for regenerating tissue in vivo. The tension in the core can also lead the fibres of the matrix to align. The combination of cellular alignment and substrate alignment serves to guide cellular regrowth in a subject.
As described in WO2004/087231, the biopolymer matrix is preferably a collagen matrix. Cells used to seed the matrix align and contract but do not proliferate to form organised tissue. The list of cells given in the publication as being of use includes Schwann cells. An embodiment of the guide may also include cells from the tissue of interest seeded within the matrix, and which will grow and be guided by the contractile cells.
The guide as described in this publication needs to remain tethered within the sheath in order to retain tension and alignment of the cells. This reduces the utility and versatility of the device.
Georgiou et al, “Engineered neural tissue for peripheral nerve repair”, Biomaterials 34 (2013) 7335-7343 describe an alternative technique in which sheets of matrix are prepared which are tethered to a mould. Seeding the matrix with Schwann cells leads to tension generation and cell self-alignment. The matrix is then removed from the mould, and partially dehydrated by removal of interstitial fluid. This results in a more robust sheet of anisotropic matrix seeded with Schwann cells. The sheet can be rolled into rods and implanted in experimental subjects to assess neural regrowth. The authors conclude that the rods are able to promote neural regrowth, and that the presence of live Schwann cells is important for clinical activity.
However, a major barrier to putting this into the clinic is to identify an available source of suitable cells. There is no suitable source of human Schwann cells. Stem cells from bone marrow or adipose tissue may be differentiated into cells with characteristics similar to Schwann cells, but there are challenges with clinical delivery, there may be a need for tissue matching, (allogeneic nerve autografts are known to provoke immune response and rejection). Use of autologous cells would involve much more complex processing, with logistical issues (cell shipping for processing, patient availability for cell harvest and return) and a high cost of goods to expand and differentiate individual patient's cells. It would be desirable to provide a technique using an alternate source of cells, preferably one with similar efficacy to Schwann cells.